Recent advances in molecular biology and the imaging sciences have created an historic opportunity to non-invasively probe cellular and molecular events associated with the ever-expanding myriad of new pathologic-related genes and proteins in vivo in both animas and humans. There exists a significant opportunity to bridge this great divide between in vitro and in vivo studies in cancer research through the development of novel molecular imaging approaches. This proposal will lead to the development of a novel imaging strategy designed by the collaborative effort of experts in imaging, tumor biology and molecular biology. We have identified a significant and relatively unexplored area of imaging caspase activity through the use of novel DNA molecules designed to produce a specific protein. This DNA molecule codes for a fusion between HSVtk and the estrogen receptor regulatory domain. Based on our previous results we propose that this fusion will lead to silencing of the HSV-tk protein and that subsequent cleavage of the fusion in a caspase-3 dependent manner (during apoptosis) will release the HSV-tk thus activating it. The presence of active HSVtk can now be used to image cells that possess active caspase-3. PROPOSED COMMERCIAL APPLICATION: Apoptosis has been implicated in a wide variety of human diseases. The development of drugs that specifically target enzymes involved in the apoptotic cascade is a vibrant and dynamic research area. The ability to non-invasively image the effectiveness of these drugs in vivo would be a breakthrough that would have significant market applications.